VM3A_BOTAL
ID VM3A_BOTAL Reviewed; 196 AA.
AC P0C6R9;
DT 18-MAR-2008, integrated into UniProtKB/Swiss-Prot.
DT 11-DEC-2013, sequence version 2.
DT 03-AUG-2022, entry version 54.
DE RecName: Full=Zinc metalloproteinase-disintegrin-like alternagin;
DE EC=3.4.24.-;
DE AltName: Full=Snake venom metalloproteinase;
DE Short=SVMP;
DE Contains:
DE RecName: Full=Disintegrin-like alternagin-C;
DE Short=Alt-C;
DE Flags: Fragment;
OS Bothrops alternatus (Urutu) (Rhinocerophis alternatus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Lepidosauria; Squamata; Bifurcata; Unidentata; Episquamata; Toxicofera;
OC Serpentes; Colubroidea; Viperidae; Crotalinae; Bothrops.
OX NCBI_TaxID=64174;
RN [1]
RP PROTEIN SEQUENCE, FUNCTION (ALTERNAGIN AND ALTERNAGIN-C), CATALYTIC
RP ACTIVITY, AND ACTIVITY REGULATION.
RC TISSUE=Venom;
RX PubMed=11368322; DOI=10.1006/abbi.2000.2120;
RA Souza D.H.F., Iemma M.R.C., Ferreira L.L., Faria J.P., Oliva M.L.V.,
RA Zingali R.B., Niewiarowski S., Selistre-de-Araujo H.S.;
RT "The disintegrin-like domain of the snake venom metalloprotease alternagin
RT inhibits alpha2beta1 integrin-mediated cell adhesion.";
RL Arch. Biochem. Biophys. 384:341-350(2000).
RN [2]
RP FUNCTION ON NEUTROPHILS (ALTERNAGIN-C).
RC TISSUE=Venom;
RX PubMed=14653807; DOI=10.1046/j.1432-1033.2003.03867.x;
RA Mariano-Oliveira A., Coelho A.L.J., Terruggi C.H.B.,
RA Selistre-de-Araujo H.S., Barja-Fidalgo C., De Freitas M.S.;
RT "Alternagin-C, a nonRGD-disintegrin, induces neutrophil migration via
RT integrin signaling.";
RL Eur. J. Biochem. 270:4799-4808(2003).
RN [3]
RP FUNCTION ON ENDOTHELIAL CELLS (ALTERNAGIN-C).
RC TISSUE=Venom;
RX PubMed=14766757; DOI=10.1074/jbc.m311771200;
RA Cominetti M.R., Terruggi C.H.B., Ramos O.H.P., Fox J.W.,
RA Mariano-Oliveira A., De Freitas M.S., Figueiredo C.C., Morandi V.,
RA Selistre-de-Araujo H.S.;
RT "Alternagin-C, a disintegrin-like protein, induces vascular endothelial
RT cell growth factor (VEGF) expression and endothelial cell proliferation in
RT vitro.";
RL J. Biol. Chem. 279:18247-18255(2004).
RN [4]
RP FUNCTION (ALTERNAGIN-C).
RC TISSUE=Venom;
RX PubMed=16172743; DOI=10.1590/s0100-879x2005001000007;
RA Selistre-de-Araujo H.S., Cominetti M.R., Terruggi C.H.B.,
RA Mariano-Oliveira A., De Freitas M.S., Crepin M., Figueiredo C.C.,
RA Morandi V.;
RT "Alternagin-C, a disintegrin-like protein from the venom of Bothrops
RT alternatus, modulates alpha2beta1 integrin-mediated cell adhesion,
RT migration and proliferation.";
RL Braz. J. Med. Biol. Res. 38:1505-1511(2005).
RN [5]
RP FUNCTION ON ANGIOGENESIS (ALTERNAGIN-C).
RX PubMed=17428438; DOI=10.1016/j.abb.2007.02.021;
RA Ramos O.H.P., Terruggi C.H.B., Ribeiro J.U., Cominetti M.R.,
RA Figueiredo C.C., Berard M., Crepin M., Morandi V., Selistre-de-Araujo H.S.;
RT "Modulation of in vitro and in vivo angiogenesis by alternagin-C, a
RT disintegrin-like protein from Bothrops alternatus snake venom and by a
RT peptide derived from its sequence.";
RL Arch. Biochem. Biophys. 461:1-6(2007).
RN [6]
RP FUNCTION ON MMP-2 MRNA AND GELATINOLYTIC ACTIVITY (ALTERNAGIN-C).
RX PubMed=18761031; DOI=10.1016/j.toxicon.2008.07.018;
RA Durigan J.L.Q., Peviani S.M., Russo T.L., Delfino G.B., Ribeiro J.U.,
RA Cominetti M.R., Selistre-de-Araujo H.S., Salvini T.F.;
RT "Effects of alternagin-C from Bothrops alternatus on gene expression and
RT activity of metalloproteinases in regenerating skeletal muscle.";
RL Toxicon 52:687-694(2008).
CC -!- FUNCTION: [Zinc metalloproteinase-disintegrin-like alternagin]:
CC hemorrhagic protease that acts as a potent inhibitor of collagen-
CC induced adhesion by blockage of alpha-2/beta-1 (ITGA2/ITGB1) integrin.
CC Cleaves at Leu-|-Met bonds (PubMed:11368322).
CC {ECO:0000269|PubMed:11368322}.
CC -!- FUNCTION: Disintegrin alternagin-C: potent inhibitor of the collagen
CC binding to alpha-2/beta-1 (ITGA2/ITGB1) integrin. Has a chemotactic
CC activity on neutrophils and this effect involves actin cytoskeleton
CC rearrangement, FAK, PI3-kinase and Erk-2 activities. Induces
CC endothelial cell proliferation, and these effects are mediated at least
CC in part by an increased expression of vascular endothelial growth
CC factor (VEGF). In injured muscles, reduces both MMP-2 mRNA and
CC gelatinolytic activity, suggesting that it changes the overall balance
CC of extracellular matrix protein turnover during muscle regeneration. In
CC low concentrations, induces formation of new vessels and up-regulates
CC the expression of VEGF receptor 2 (KDR) without affecting VEGF receptor
CC 1 (FLT1) expression. In high concentrations, strongly inhibits
CC angiogenesis, and the expression of both receptors is down-regulated.
CC Has very low plasma clotting activity.
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- ACTIVITY REGULATION: Inhibited by EDTA. {ECO:0000269|PubMed:11368322}.
CC -!- SUBUNIT: Monomer. {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Secreted.
CC -!- TISSUE SPECIFICITY: Expressed by the venom gland.
CC -!- PTM: The N-terminus of alternagin is blocked.
CC -!- MISCELLANEOUS: [Zinc metalloproteinase-disintegrin-like alternagin]:
CC does not present any fibrinogen-clotting activity and does not bind to
CC alpha-IIb/beta-3 (ITGA2B/ITGB3), alpha-1/beta-1 (ITGA1/ITGB1), alpha-
CC 5/beta-1 (ITGA5/ITGB1), alpha-4/beta-1 (ITGA4/ITGB1), alpha-V/beta-3
CC (ITGAV/ITGB3) and alpha-9/beta-1 (ITGA9/ITGB1) integrins.
CC {ECO:0000305|PubMed:11368322}.
CC -!- SIMILARITY: Belongs to the venom metalloproteinase (M12B) family. P-III
CC subfamily. P-IIIb sub-subfamily. {ECO:0000305}.
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DR MEROPS; M12.335; -.
DR GO; GO:0005576; C:extracellular region; IEA:UniProtKB-SubCell.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008237; F:metallopeptidase activity; IEA:UniProtKB-KW.
DR GO; GO:0090729; F:toxin activity; IEA:UniProtKB-KW.
DR GO; GO:0001525; P:angiogenesis; IEA:UniProtKB-KW.
DR GO; GO:0030154; P:cell differentiation; IEA:UniProtKB-KW.
DR GO; GO:0006935; P:chemotaxis; IEA:UniProtKB-KW.
DR GO; GO:0006508; P:proteolysis; IEA:UniProtKB-KW.
DR Gene3D; 4.10.70.10; -; 1.
DR InterPro; IPR006586; ADAM_Cys-rich.
DR InterPro; IPR001762; Disintegrin_dom.
DR InterPro; IPR036436; Disintegrin_dom_sf.
DR Pfam; PF08516; ADAM_CR; 1.
DR Pfam; PF00200; Disintegrin; 1.
DR PRINTS; PR00289; DISINTEGRIN.
DR SMART; SM00608; ACR; 1.
DR SMART; SM00050; DISIN; 1.
DR SUPFAM; SSF57552; SSF57552; 1.
DR PROSITE; PS50214; DISINTEGRIN_2; 1.
PE 1: Evidence at protein level;
KW Angiogenesis; Calcium; Cell adhesion impairing toxin; Chemotaxis;
KW Developmental protein; Differentiation; Direct protein sequencing;
KW Disulfide bond; Hemorrhagic toxin; Hemostasis impairing toxin; Hydrolase;
KW Metal-binding; Metalloprotease; Protease; Secreted; Toxin.
FT CHAIN <1..>196
FT /note="Zinc metalloproteinase-disintegrin-like alternagin"
FT /id="PRO_0000326269"
FT CHAIN 1..>196
FT /note="Disintegrin-like alternagin-C"
FT /id="PRO_0000326270"
FT DOMAIN 4..90
FT /note="Disintegrin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT MOTIF 68..70
FT /note="D/ECD-tripeptide"
FT BINDING 6
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 9
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 11
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 13
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 16
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 19
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="1"
FT /evidence="ECO:0000250"
FT BINDING 70
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 71
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 73
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 85
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT BINDING 86
FT /ligand="Ca(2+)"
FT /ligand_id="ChEBI:CHEBI:29108"
FT /ligand_label="2"
FT /evidence="ECO:0000250"
FT DISULFID 7..36
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 7..26
FT /note="In disintegrin-like alternagin-C; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 18..36
FT /note="In disintegrin-like alternagin-C; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 18..31
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 20..26
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 30..53
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 44..50
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 49..75
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 62..82
FT /note="In both disintegrin-like alternagin-C and zinc
FT metalloproteinase-disintegrin-like alternagin"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 69..101
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 69..94
FT /note="In disintegrin-like alternagin-C; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 94..106
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 101..106
FT /note="In disintegrin-like alternagin-C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 114..164
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 114..129
FT /note="In disintegrin-like alternagin-C; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 129..175
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 142..152
FT /note="In zinc metalloproteinase-disintegrin-like
FT alternagin; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 152..159
FT /note="In disintegrin-like alternagin-C; alternate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT DISULFID 164..175
FT /note="In disintegrin-like alternagin-C"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00068"
FT UNSURE 30..31
FT /note="Assigned by comparison with orthologs"
FT UNSURE 82
FT /note="Assigned by comparison with orthologs"
FT UNSURE 152
FT /note="Assigned by comparison with orthologs"
FT NON_TER 1
FT NON_TER 196
SQ SEQUENCE 196 AA; 21731 MW; D7031E021D1479C2 CRC64;
IISPPVCGNE LLEVGEECDC GTPENCQNXC CDAATCKLKS GSQCGHXDCC EQCKFTKSGT
ECRASMSECD PAEHCTGQSX XCXXDVFHKN GQPCLDNYGY CYNGNCPIMY HAQCYALFGA
DVYEAEDSCF KDNQKGNYYG YCRKENXXXX XCXXXDVKCG RLYCKDNSPK QNNPCKMFYS
NDDEHKGNVL PGTKCE
